This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pentamidine is a clinically available anti-protozoal agent, which also inhibits the interaction of wild type p53 and S100B;these are frequently expressed in melanomas. The primary objective is to determine the response rate of relapsed and/or refractory melanoma that has previously been defined to express detectable S100B and to have a wild-type p53 mutation. Secondary objectives include assessment of toxicities, observation of time to disease progression, and observation of effect of drug treatment on expression of S100B and p53.